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3 weeks ago Solid tumor

Chinese ADC Drug Targeting B7-H3 Approved for Clinical Trials!

ADC

#ADC #Immunotherapy#B7H3 #LungCancer #HeadAndNeckCancer #ADCDrug

On September 20, the China National Medical Products Administration (NMPA) approved BeiGene’s innovative anti-cancer drug, BGB-C354, for clinical trials. This exciting news marks the first approval for clinical research of this novel molecule in China. BGB-C354 is an Antibody-Drug Conjugate (ADC) specifically designed to target B7-H3, a protein often overexpressed in various cancers such as lung cancer, prostate cancer, breast cancer, and squamous cell carcinoma of the head and neck.

BGB-C354 holds significant promise for treating patients with advanced solid tumors, particularly lung cancer and head and neck squamous cell carcinoma (HNSCC). B7-H3 has gained attention as a key anti-cancer target, with its high expression often linked to poor prognosis. By leveraging the power of ADC technology, BGB-C354 aims to selectively deliver potent anti-cancer drugs directly to tumor cells, minimizing damage to healthy cells.

BeiGene has already initiated a Phase 1 clinical trial in the US and Australia, evaluating the safety, tolerability, and preliminary anti-tumor activity of BGB-C354 as a monotherapy and in combination with anti-PD-1 antibody, Tislelizumab. This recent approval sets the stage for the commencement of clinical trials in China.

Globally, B7-H3-targeted therapies are advancing rapidly. Companies like Daiichi Sankyo, Merck, and GSK are pushing the boundaries with their ADCs, entering Phase 2 and 3 clinical trials. The approval of BGB-C354 marks a significant step in advancing cancer treatment options in China, offering new hope for patients with difficult-to-treat cancers.

To assess whether the condition is suitable for clinic therapy, you can submit Advanced Medicine in China for preliminary evaluation!

WhatsApp: +8613717959070

Https://wa.me/+8613717959070

Email: doctor.huang@globecancer.com

#CancerTreatment #ClinicalTrials #BeiGene #OncologyBreakthrough #PharmaInnovation #CancerResearch

3 weeks ago Solid tumor

The Lancet | Chinese Medical Team: A New Breakthrough in the Treatment of Limited-stage Small Cell Lung Cancer!

High-dose Accelerated Hyperfractionated Radiotherapy Helps Improve Treatment Efficacy

Lung Cancer

#SCLC #SmallcelllungCancer #LungCancer #Lancet #LSSCLC

Small-cell lung cancer (SCLC) is a highly aggressive malignancy, accounting for 15% of all lung cancer cases. Among these, one-third are diagnosed with limited-stage SCLC (LS-SCLC), where the disease is confined to one side of the chest. For the past two decades, the standard treatment for LS-SCLC has been concurrent chemoradiotherapy, yet patients have seen little improvement in survival outcomes, with median survival ranging from 25-30 months.

A New Hope for LS-SCLC Patients

A recent study led by a team of Chinese researchers has shed light on a new treatment strategy. Published in The Lancet Respiratory Medicine, this multicenter, open-label, randomized phase III trial demonstrated that a high-dose, accelerated, hyperfractionated thoracic radiotherapy (54 Gy/30 fractions) combined with chemotherapy significantly improves overall survival (OS) and progression-free survival (PFS) for LS-SCLC patients. Importantly, this breakthrough treatment does not increase toxicity compared to the standard 45 Gy/30 fractions regimen.

Study Design and Methodology

The trial, conducted between 2017 and 2021, enrolled 224 patients across 16 hospitals in China. The patients, aged 18-70, had histologically or cytologically confirmed LS-SCLC and had either not yet received treatment or had undergone 1-2 cycles of chemotherapy. After chemotherapy, they were randomly assigned to receive either the high-dose (54 Gy/30 fractions) or standard-dose (45 Gy/30 fractions) thoracic radiotherapy, delivered twice daily over three weeks. Both groups also underwent four cycles of chemotherapy and, if responsive, prophylactic cranial irradiation (PCI) to prevent metastasis.

Improved Survival Outcomes

The study’s results were groundbreaking. Patients in the high-dose group showed a remarkable improvement in OS, with a median survival of 60.7 months, compared to 39.5 months in the standard-dose group. Additionally, the high-dose group saw a 45% reduction in the risk of death. Two-year survival rates also favored the high-dose group, with 76% of patients alive at two years, compared to 54% in the standard-dose group.

Progression-free survival was similarly improved, with the high-dose group experiencing a median PFS of 30.5 months, significantly longer than the 16.7 months observed in the standard-dose group. This translates to a 30% reduction in the risk of disease progression or death.

Safety and Tolerability

Despite the higher radiotherapy dose, the incidence of adverse effects between the two groups was comparable. The most common severe side effects were neutropenia, thrombocytopenia, and anemia, which occurred at similar rates in both groups. The occurrence of acute radiation-induced toxicity, such as esophagitis and radiation pneumonitis, also showed no significant differences. Importantly, there were no cases of severe late-stage toxicity, such as grade 3 esophageal stenosis or pulmonary fibrosis.

Clinical Implications and Future Directions

This study demonstrates that high-dose, accelerated hyperfractionated thoracic radiotherapy can significantly improve the prognosis of LS-SCLC patients without increasing treatment toxicity. It provides a new first-line treatment option that offers hope for longer survival. These findings may shift the clinical landscape, offering a viable alternative to the current standard of care.

As research continues to explore combining this high

A groundbreaking study led by a Chinese medical team has demonstrated that high-dose accelerated hyperfractionated chest radiotherapy (54 Gy/30 fractions) combined with chemotherapy significantly improves the overall survival (OS) of patients with limited-stage small-cell lung cancer (LS-SCLC). The research was published in The Lancet Respiratory Medicine on August 12, 2024. Compared to the standard dose of 45 Gy/30 fractions, the 54 Gy regimen increased OS without raising treatment toxicity, marking a potential shift in LS-SCLC treatment strategy.

Key Findings of the Study

LS-SCLC, a highly aggressive form of lung cancer, affects around 15% of all lung cancer patients, with one-third of them diagnosed at a limited stage. Traditionally, concurrent chemoradiotherapy (CRT) has been the preferred treatment option for LS-SCLC, yet the median survival rate has remained stagnant at around 25-30 months over the past two decades. The new study, however, highlights the efficacy of using higher doses of radiation to improve outcomes.

This phase III clinical trial was conducted across 16 hospitals in China between June 2017 and April 2021, involving 224 LS-SCLC patients. The trial compared two groups: a high-dose radiotherapy group (54 Gy/30 fractions twice daily) and a standard-dose group (45 Gy/30 fractions twice daily). Patients were treated with four cycles of chemotherapy and monitored through regular follow-ups. The results were remarkable.

Overall Survival: The high-dose group had a significantly extended median OS of 60.7 months compared to 39.5 months in the standard-dose group, reducing the risk of death by 45%.

Progression-Free Survival (PFS): The median PFS was also improved in the high-dose group, standing at 30.5 months compared to 16.7 months in the standard-dose group, with a 30% reduction in the risk of disease progression or death.

Safety: Despite the higher radiation dose, there was no increase in severe treatment-related side effects, such as neutropenia, thrombocytopenia, or radiation-induced pneumonia. Both groups exhibited similar rates of acute and long-term radiation toxicity.

Why Is This Study Important?

The study’s findings suggest that 54 Gy/30 fractions, delivered twice daily, may become a new standard of care for LS-SCLC patients. This approach significantly extends survival while maintaining a similar safety profile to the current standard dose. Moreover, with a two-year OS rate of 76% in the high-dose group, compared to 54% in the standard-dose group, the potential for long-term remission appears much greater.

A New Era in LS-SCLC Treatment?

While the current trial focused on radiotherapy and chemotherapy alone, future studies could explore combining this high-dose radiotherapy with immunotherapy. Recent breakthroughs, such as the ADRIATIC trial, have shown that immunotherapy following CRT can further improve survival outcomes for LS-SCLC patients. However, the safety of combining high-dose radiotherapy with immunotherapy needs further investigation due to potential risks like radiation-induced pneumonitis.

In conclusion, this study has paved the way for a new treatment option in LS-SCLC, offering hope for improved survival rates without additional toxicity. It marks a significant milestone in the battle against this aggressive form of lung cancer, providing a valuable alternative to the long-standing standard treatments.

To assess whether the condition is suitable for clinic therapy, you can submit Advanced Medicine in China for preliminary evaluation!

WhatsApp: +8613717959070

Https://wa.me/+8613717959070

Email: doctor.huang@globecancer.com

#LungCancerTreatment #SCLCTherapy #CancerResearch #MedicalBreakthrough #ChinaHealthcare #Oncology #LungCancerSurvival #Radiotherapy #CancerCare #ClinicalTrials

4 weeks ago Solid tumor

Published in Cell Journal | Breakthrough in dMMR Metastatic Colorectal Cancer Treatment: Chinese Research Garners International Recognition

Colorectal Cancer

#ColorectalCancer #PD1Antibody #dMMR #cell #cellpress #Med #PD-1 #CellJournal

A Chinese medical team has made a significant breakthrough in the treatment of dMMR (deficient mismatch repair) metastatic colorectal cancer. Recently, their latest research findings were published in the Med journal, a subsidiary of Cell, offering new treatment hope for patients with advanced colorectal cancer.

The study revealed that the combination of PD-1 antibody immunotherapy with COX inhibitors, drugs commonly used for anti-inflammatory treatment, significantly improved treatment effectiveness. This innovative strategy could substantially increase survival chances for patients with advanced colorectal cancer.

Colorectal cancer is the second most common cancer in China, and its incidence is on the rise. While PD-1 antibody immunotherapy has brought hope to some patients, its success rate is only 45%. Approximately 30% of dMMR metastatic colorectal cancer patients are resistant to PD-1 treatment. Therefore, the Chinese team explored combining PD-1 immunotherapy with COX inhibitors (such as celecoxib and aspirin) to overcome this resistance.

The team’s Phase 2 clinical trial yielded remarkable results. Among the 30 patients who received the combination therapy, the overall response rate was 73.3%, a 30% improvement over PD-1 monotherapy. After more than four years of follow-up, 65% of patients achieved progression-free survival, and 90% were still alive. Four patients reached complete remission, while 11 others underwent surgery, with 10 showing complete pathological remission.

In addition to the notable clinical outcomes, genomic and immunological analysis revealed that high expression of the TAPBP protein was associated with better treatment results. This discovery opens new avenues for the development of biomarkers to predict treatment response and for personalized treatment plans in the future.

Following the publication of the study, it attracted significant attention from the international medical community. Experts from Memorial Sloan Kettering Cancer Center in the U.S. wrote a commentary in the Med journal, highly praising the innovative therapy. They noted that the combination of COX inhibitors with PD-1 treatment not only increased the complete remission rate but also reduced immune suppression signals in the tumor microenvironment, enhancing the effectiveness of PD-1 therapy, with manageable side effects.

This research offers new hope for dMMR metastatic colorectal cancer patients worldwide, and further large-scale clinical trials are expected to confirm its efficacy. The combination of COX inhibitors with PD-1 immunotherapy could become a safe and effective treatment option for dMMR metastatic colorectal cancer patients, providing hope for long-term survival.

🎉🎉To assess whether the condition is suitable for CAR-T or clinic therapy, you can submit Advanced Medicine in China for preliminary evaluation!
WhatsApp: +8613717959070

（Https://wa.me/+8613717959070）
Email: doctor.huang@globecancer.com

#CancerResearch #MedicalInnovation #GlobalHealth #Immunotherapy #Colorectal #COXInhibitors

2 months ago Myeloma

Groundbreaking Results for Chinese CAR-T Therapy: 86% Response Rate of BCMA/GPRC5D Dual-Target Treatment Multiple myeloma

Groundbreaking Results for Chinese CAR-T Therapy: 86% Response Rate of BCMA/GPRC5D Dual-Target Treatment

Multiple myeloma

#MultipleMyeloma #ChineseCART #BCMA #GPRC5D #DualTarget #MM #RRMM

Multiple myeloma (MM) is a challenging blood cancer, particularly in relapsed/refractory (R/R) cases. While therapies like proteasome inhibitors, immunomodulators, CD38 monoclonal antibodies, and stem cell transplants have improved outcomes for newly diagnosed patients, treatment-resistant forms of MM remain a serious concern. A new therapeutic approach combining two targets, BCMA and GPRC5D, may provide a breakthrough solution.

BCMA has long been a key target for treating R/R MM due to its expression in malignant plasma cells. However, BCMA-targeted therapies face limitations, including tumor cells losing or downregulating BCMA, leading to disease recurrence. This is where GPRC5D, a protein highly expressed in MM cells and linked to poor prognosis, comes in. By targeting both BCMA and GPRC5D, researchers aim to overcome the limitations of single-target therapies.

A collaboration between a leading Chinese hospital and research institutions has now delivered promising results. A Phase I clinical trial involving 21 patients with R/R MM using the dual-target BCMA/GPRC5D CAR-T cell therapy reported an overall response rate (ORR) of 86%, with 75% of patients achieving a complete response (CR). Notably, even patients whose cancer cells lacked BCMA or GPRC5D expression showed significant improvement, underscoring the versatility of this treatment.

Key Results from the Study:

– 21 patients with advanced, heavily pre-treated R/R MM participated.

– Of the 12 patients who received the optimal dosage of 2.0×10⁶ CAR-T cells/kg, 86% showed clinical response, with 75% achieving complete remission.

– Importantly, patients with BCMA or GPRC5D-negative cancer cells also responded well to treatment.

– The treatment was well-tolerated, with manageable side effects, including 71% of patients experiencing mild to moderate cytokine release syndrome (CRS).

This trial, published in The Lancet Haematology, represents a major step forward in MM treatment. The dual-target approach addresses the limitations of BCMA-targeted therapies, offering new hope to patients who have exhausted conventional options.

Looking ahead, this innovative therapy could reshape the future of multiple myeloma treatment, offering a powerful new tool in the fight against this complex disease.

🎉🎉To assess whether the condition is suitable for CAR-T or clinic therapy, you can submit Advanced Medicine in China for preliminary evaluation!
WhatsApp: +8613717959070
Email: doctor.huang@globecancer.com

#CancerResearch #MultipleMyeloma #CAR_TTherapy #MedicalInnovation #OncologyBreakthrough

2 months ago Solid tumor

Breaking Ground: The First Nectin-4 Targeted ADC Approved in China – Urothelial Carcinoma

Breaking Ground: The First Nectin-4 Targeted ADC Approved in China

Urothelial Carcinoma

#UrothelialCarcinoma #Nectin4 #ADC

On August 19, the National Medical Products Administration (NMPA) of China officially approved the innovative antibody-drug conjugate (ADC), Enfortumab Vedotin, developed by Astellas and Pfizer. This groundbreaking approval marks the first Nectin-4 targeted ADC to receive approval in China, providing a new treatment option for patients with locally advanced or metastatic urothelial carcinoma who have previously undergone treatment with PD-1/PD-L1 inhibitors and platinum-based chemotherapy.

Pioneering Nectin-4 Targeting

Nectin-4, a protein found on the surface of cells, is highly expressed in bladder cancer. Enfortumab Vedotin, co-developed by Astellas and Seagen (a Pfizer subsidiary), is a first-in-class ADC that directly targets Nectin-4. By binding to cells expressing this protein, the drug delivers the potent anti-tumor agent monomethyl auristatin E (MMAE) into the cells, halting cell proliferation and inducing programmed cell death.

This ADC had already secured approvals in the United States, Japan, and the European Union for treating urothelial carcinoma. Now, with its approval in China, Enfortumab Vedotin stands as a beacon of hope for Chinese patients battling this challenging form of cancer.

Clinical Evidence from China: The EV-203 Study

The approval in China was based on data from the EV-203 study (NCT04995419), a phase II, single-arm, open-label, multi-center clinical trial conducted in China. The trial assessed the efficacy, safety, and pharmacokinetics of Enfortumab Vedotin in Chinese patients with locally advanced or metastatic urothelial carcinoma who had been treated with PD-1/PD-L1 inhibitors and platinum-based chemotherapy.

The study enrolled 40 Chinese patients, with the primary endpoint being the independent review committee (IRC) confirmed objective response rate (ORR). Results presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting revealed:

– An IRC-confirmed ORR of 37.5%, including one complete response (2.5%) and 14 partial responses (35.0%).

– A disease control rate (DCR) of 82.5% as per investigator assessment and 72.5% as per IRC evaluation.

– Median progression-free survival (PFS) was 4.24 months according to investigators and 4.67 months per IRC assessment.

– Median overall survival (OS) had not been reached at the time of analysis, with a median follow-up of 6.5 months.

The safety profile was manageable, with most treatment-related adverse events (TRAEs) being grade 1-2. These results underscore Enfortumab Vedotin’s meaningful clinical activity and a favorable benefit-risk profile in this patient population.

Looking Ahead: Expanding Treatment Options

Astellas is also progressing with a second indication for Enfortumab Vedotin in China. In March 2024, the company submitted an application for its use in combination with the PD-1 inhibitor pembrolizumab as a first-line treatment for adults with locally advanced or metastatic urothelial carcinoma who have not previously received treatment. Insight data predicts that this application could be approved as early as the third quarter of 2025.

Beyond Enfortumab Vedotin, there are over a dozen Nectin-4 targeted ADC projects under development in China. Among them, the most advanced is 9MW2821 from Mabwell, currently in phase III trials for urothelial carcinoma. Other promising candidates include SHR-A2102 from Hengrui, SYS6002 from CSPC, SKB410 from Kelun-Biotech, ADRX-0706 from Dizal/Adcentrx, and BAT8007 from Bio-Thera, all of which have entered clinical stages.

To assess whether the condition is suitable for CAR-T or clinic therapy, you can submit Advanced Medicine in China for preliminary evaluation!

WhatsApp: +8613717959070

Email: doctor.huang@globecancer.com

**#Nectin4ADC #CancerResearch #UrothelialCarcinoma #InnovativeMedicine #ChinaPharma #EnfortumabVedotin #ADC #PD1 #PDL1 #NEctin4

2 months ago Lymphoma

Chinese Medical Team Research: 64.6% Complete Remission Rate, Over Half of Patients Progression-Free for More Than Two Years! Targeted Therapy Combined with Chemotherapy is Safe and Effective as First-Line Treatment for Lymphoma

Lymphoma

Peripheral T-cell lymphoma (PTCL) is a group of highly aggressive and heterogeneous diseases with poor prognosis. The standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) is widely used as first-line treatment for PTCL. Previous studies have confirmed the safety and efficacy of combining various targeted drugs with CHOP (CHOPX) for PTCL treatment. However, there are multiple PTCL subtypes with different mutations, such as TP53, TET2, KMT2D, and CREBBP/EP300, and evidence is still lacking regarding the effectiveness of these combined treatment regimens in patients with specific genetic mutations.

Recently, a Chinese study published in The Lancet Regional Health–Western Pacific showed that selecting targeted therapies based on specific genetic mutations, combined with CHOP as a first-line treatment for PTCL, demonstrated good efficacy and safety. Compared to standard CHOP, CHOPX treatment achieved a higher complete remission rate and longer progression-free survival. This study was conducted by a Chinese medical team.

This was an open-label, multi-center, non-randomized, external-controlled phase 2 clinical trial (code-named GUIDANCE-03) conducted across seven medical centers in China. The trial compared the efficacy and safety of targeted drug combinations based on specific genetic mutations with CHOP (CHOPX) versus CHOP alone in newly diagnosed PTCL patients.

A total of 96 newly diagnosed PTCL patients (aged ≥18 years, median age 63 years) were enrolled in the study, with 48 patients in each group (CHOPX and CHOP). Genetic sequencing results showed that 93 patients (96.9%) carried genetic mutations. Patients in the CHOPX group received standard CHOP treatment during the first treatment cycle. Starting from the second cycle, targeted drugs were added based on the patient’s specific genetic mutations: decitabine (for TP53 mutations), azacitidine (for TET2/KMT2D mutations), chidamide (for CREBBP/EP300 mutations), and lenalidomide (for patients without these mutations), with a total of six treatment cycles. Patients in the CHOP group received six cycles of CHOP treatment.

The primary endpoint of the study was the complete remission rate (CRR) at the end of treatment. Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. The analysis results showed:

– At the end of treatment, the CRR of the CHOPX group was superior to that of the CHOP group. Compared to the CHOP group, the CHOPX group saw an approximate 30% improvement in CRR (64.6% vs. 33.3%, OR 0.27, 95% CI 0.12-0.64; P=0.004), achieving the primary endpoint of the study.

– For secondary endpoints, the ORR of the CHOPX group was better than that of the CHOP group (66.7% vs. 52.1%).

– During a median follow-up period of 24.3 months, the median PFS of the CHOPX group was significantly longer than that of the CHOP group (25.5 months vs. 9.0 months; HR 0.57, 95% CI 0.34-0.98; P=0.041), with a 43% reduction in the risk of disease progression or death. The 2-year PFS rates for the two groups were 53.2% (95% CI 38.7-67.7) and 28.0% (95% CI 13.6-42.3), respectively.

In terms of OS, the median OS for the CHOPX group has not yet been reached, while the median OS for the CHOP group was 30.9 months. The CHOPX group showed a trend toward improved OS, but the current statistical results are not significant (HR 0.55, 95% CI 0.28-1.10; P=0.088). The 2-year OS rates for the two groups were 68.0% and 60.8%, respectively.

Regarding safety, neutropenia was the most common adverse event in both the CHOPX and CHOP groups (82% in the CHOPX group and 73% in the CHOP group). The most common grade 3-4 hematologic adverse event in both groups was neutropenia, and the most common grade 3-4 non-hematologic adverse event was infection. In the CHOPX group, 65% (31 patients) reported neutropenia, but no patients experienced prolonged neutropenia (>14 days) or required dose adjustments of the targeted drugs, and 10% (5 patients) experienced infections. In the CHOP group, these proportions were 52% (25 patients) and 4% (2 patients), respectively.

In conclusion, the study results indicate that different targeted drugs combined with CHOP demonstrate good efficacy and safety. These findings provide preliminary evidence supporting the use of CHOPX as a first-line treatment for PTCL patients with different genetic mutations, and suggest that biomarker-driven treatment strategies are feasible and worth further exploration in the future.

To assess whether the condition is suitable for CAR-T or clinic therapy, you can submit Advanced Medicine in China for preliminary evaluation!

WhatsApp: +8613717959070

Email: doctor.huang@globecancer.com

#CancerResearch #LymphomaTreatment #PTCL #TargetedTherapy #Chemotherapy #MedicalBreakthrough #Oncology #ClinicalTrials #ChineseMedicine #CancerSurvivorship #HealthcareInnovation #PrecisionMedicine #CancerTreatment #MedicalResearch #CHOPTherapy #OncologyUpdates #CancerCare

2 months ago Hematological Neoplasms

Blood Cancer Solution Including leukemia, lymphoma, multiple myeloma, and others.

Blood Cancer Solution

Including leukemia, lymphoma, multiple myeloma, and others.

Blood Cancer

#leukemia #lymphoma #multiplemyeloma

#Hematologic malignancies are a group of malignant diseases originating from hematopoietic cells, often affecting the bone marrow, blood, and various organs and tissues throughout the body. Common types of hematologic malignancies include leukemia, myelodysplastic syndromes, lymphomas, multiple myeloma, and myeloproliferative neoplasms.

The causes of these diseases are complex, involving genetic mutations, immune abnormalities, radiation exposure, contact with harmful chemicals, infections, and hereditary factors. Additionally, poor lifestyle habits, high levels of stress, and environmental factors can also increase the risk of developing these conditions.

With an aging population and advancements in medical technology, the incidence of hematologic malignancies has been rising globally. In China, the incidence and mortality rates of leukemia and lymphoma are now among the top ranks of all malignancies.

However, hematologic malignancies are not incurable. In recent years, the treatment methods for these diseases have seen significant progress. From traditional combination chemotherapy and radiotherapy to hematopoietic stem cell transplantation, monoclonal antibody therapy, antibody-drug conjugates, small molecule targeted therapies, and the latest immunotherapies, treatment options have become increasingly diverse and precise.

Combination chemotherapy remains a primary treatment for many hematologic malignancies, despite its significant side effects. The efficacy of these treatments cannot be ignored. Modern chemotherapy regimens are continually being refined, including the incorporation of new cytotoxic drugs and targeted therapies, as well as the use of monoclonal antibodies. Additionally, the appropriate use of antiemetics, hematopoietic growth factors, and anti-infective agents helps to mitigate adverse effects.

Hematopoietic stem cell transplantation continues to be one of the most effective treatments for certain hematologic malignancies. The development of this treatment in China has been rapid, with 170 registered transplant centers by 2020.

Monoclonal antibodies, often referred to as “biological missiles,” have a high degree of specificity and single biological activity. They have revolutionized the treatment of hematologic malignancies. Antibody-drug conjugates (ADCs) utilize monoclonal antibodies to accurately identify tumor cell markers, guiding the delivery of chemotherapy drugs for targeted treatment.

Small molecule targeted therapies work by interfering with specific genes or proteins to inhibit tumor cell growth and proliferation. Gleevec, the first small molecule targeted therapy, increased the five-year survival rate for chronic myeloid leukemia (CML) patients from 30% to 89%, marking a breakthrough in cancer treatment. Today, there are numerous small molecule targeted drugs available for the treatment of hematologic malignancies, including BCR-ABL inhibitors, BTK inhibitors, BCL-2 inhibitors, PI3K inhibitors, and XPO1 inhibitors, with many more drugs currently in clinical trials expected to become available soon.

Immunotherapy includes immune checkpoint inhibitors (such as PD-1/L1), cancer vaccines, cellular immunotherapies (such as #CART), and nonspecific immunomodulatory treatments. #CARTtherapy, in particular, has gained widespread attention as an emerging curative treatment. This approach involves extracting a patient’s T cells, modifying them outside the body to specifically recognize and attack tumor cells, and then reinfusing the modified T cells into the patient. This therapy has been successfully applied to various hematologic malignancies, including acute lymphoblastic leukemia, lymphomas, and multiple myeloma. The first patient treated with CAR-T therapy has been disease-free for 11 years.

In recent years, China has made significant advances in the treatment of hematologic malignancies. The establishment of the “Chinese Expert Consensus on the Diagnosis and Treatment of High-Risk Multiple Myeloma” and the presentation by Professor Huang He at the 2024 #EHA conference on targeting CD7 universal CAR-T therapy for T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) have shown remarkable efficacy and safety. Additionally, exciting new data from the 2024 American Society of Clinical Oncology (#ASCO) annual meeting highlighted the efficacy of Relma-cel in treating relapsed/refractory large B-cell lymphoma (R/R LBCL), with a four-year overall survival rate (#OS) of 66.7%. Particularly noteworthy is the research on multiple myeloma, where the BCMA-targeted CAR-T therapy has demonstrated deep and lasting responses, with a complete response (#CR) rate of 82.4% and a 12-month progression-free survival (#PFS) rate of 85.5%.

With the continuous development of new treatments and the emergence of new drugs, hematologic malignancies in China are no longer considered incurable diseases. Through standardized, individualized, and precise treatments, many patients with hematologic malignancies can achieve long-term disease-free survival, and even a cure, returning to normal work and life. As medicine continues to advance, every life will continue to shine brightly!

To assess whether the condition is suitable for CAR-T or clinic therapy, you can submit Advanced Medicine in China for preliminary evaluation!

WhatsApp: +8613717959070

Email: doctor.huang@globecancer.com

#HematologicMalignancies #LeukemiaAwareness #LymphomaResearch #MultipleMyeloma #BloodCancer #CancerResearch #CAR_Therapy #StemCellTransplant #Immunotherapy #TargetedTherapy #MonoclonalAntibodies #CancerTreatment #MedicalAdvancements #CancerSurvivor #HealthcareInnovation

2 months ago Lymphoma

2024 ASCO | Relma-cel Achieves a 4-Year OS Rate of 66.7% in Treating R/R LBCL, Making Lymphoma Cure Possible

Lymphoma

Over the past few decades, there have been significant advancements in the treatment of hematologic malignancies, particularly with CAR-T cell therapy. Recently, Relma-cel (relmacabtagene autoleucel) showcased promising new data at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, highlighting its remarkable efficacy in treating relapsed/refractory large B-cell lymphoma (R/R LBCL).

### Breakthrough in CAR-T Therapy

Relma-cel is a CD19-targeted CAR-T cell therapy that reprograms a patient’s own T cells to recognize and attack cancer cells. Studies have shown that Relma-cel achieves a 4-year overall survival (OS) rate of 66.7% in patients with R/R LBCL, with the rate soaring to 82.5% for those who achieve complete remission (CR). These results indicate that Relma-cel not only significantly extends survival but also increases the cure rate for these patients.

### The Power of Long-Term Follow-Up Data

The RELIANCE study, one of the largest CAR-T cell therapy studies in China, aims to evaluate the efficacy and safety of Relma-cel in R/R LBCL patients. The latest 4-year follow-up data reveals that 25 patients remain alive, and the median overall survival (OS) has not yet been reached. This milestone offers immense hope for patients and physicians, underscoring the long-term survival benefits of this therapy.

### Balancing Safety and Efficacy

Relma-cel also excels in safety. The incidence rates of ≥3 grade cytokine release syndrome (CRS) and neurotoxicity (NT) are 5.1% and 3.4%, respectively. Compared to other CD19 CAR-T cell therapies, Relma-cel effectively reduces side effects while significantly enhancing efficacy. This success is largely attributed to its unique CAR structure design, which includes a 4-1BB costimulatory domain, a CD28 transmembrane domain, and an optimized hinge region. These features enable Relma-cel to survive longer in the body and enhance its tumor-killing power.

### Future Prospects

As Relma-cel continues to expand its reach, more R/R LBCL patients are expected to benefit from this advanced treatment. Currently, Relma-cel is exploring its potential use in second-line treatment for LBCL and frontline therapy for high-risk LBCL patients. Additionally, it has shown excellent clinical value in treating relapsed/refractory follicular lymphoma (R/R FL) and mantle cell lymphoma (R/R MCL).

Relma-cel’s success not only brings new hope to lymphoma patients but also signifies a new era in the treatment of hematologic malignancies. We look forward to more research findings on Relma-cel, which will bring hope and possibilities for curing lymphoma to patients worldwide.

With Relma-cel, curing lymphoma is no longer an unattainable dream. Let’s anticipate more breakthroughs in this field, bringing new light to the lives of every patient.

🎉🎉To assess whether the condition is suitable for CAR-T or clinic therapy, you can submit Advanced Medicine in China for preliminary evaluation!

WhatsApp: +8613717959070

Email: doctor.huang@globecancer.com

#LymphomaTreatment #CAR_TTherapy #CancerResearch #RelmaCel #HopeForPatients #MedicalAdvancements #ASCO2024 #InnovativeTherapies #Survivorship #CureLymphoma

3 months ago CAR-T

2024EHA | Professor Huang He: Targeting CD7 Universal CAR-T Therapy Shows Significant Efficacy and Good Safety in Treating R/R CD7+ T-ALL/LBL Patients

The 29th Annual Meeting of the European Hematology Association (EHA) 2024 concluded successfully on June 16, 2024, in Madrid, Spain. As a premier event in the international hematology field, it showcased the latest advancements in foundational and clinical practices.

At this year’s EHA meeting, several studies from Professor Huang He’s team at the First Affiliated Hospital, Zhejiang University School of Medicine were selected. One of these studies, titled “Phase I Study of Targeting CD7 Universal CAR-T Therapy for Relapsed/Refractory CD7+ T-ALL/LBL Patients,” was featured in a poster presentation.

T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) are aggressive malignancies originating from precursor T cells, often affecting the bone marrow (BM), central nervous system (CNS), and mediastinum. Despite multiple lines of chemotherapy or allogeneic hematopoietic stem cell transplantation, some patients progress to a relapsed/refractory stage with poor prognosis, posing a significant clinical challenge. Current CAR-T cell therapies primarily target B-cell hematologic malignancies and multiple myeloma, such as CD19 CAR-T and BCMA CAR-T, while mature targets for T-cell hematologic malignancies are lacking. Preliminary research data indicate that CD7 could be a potential therapeutic target for T-cell hematologic malignancies. Based on this, the team developed a universal CAR-T product targeting CD7, named RD13-02, characterized by CRISPR/Cas9 technology to modify T-cell receptors (TCR) and CD7, creating an innovative “off-the-shelf” CAR-T cell therapy product aimed at truly achieving shelf-ready cell therapy.

The objective of this study was to evaluate the safety and efficacy of RD13-02 in treating R/R T-ALL/LBL. A total of 12 eligible R/R T-ALL/LBL patients (7 ALL, 5 LBL) were enrolled in the study, all exhibiting CD7 antigen expression. Six patients had extramedullary disease; all had blast cells in the bone marrow, with a median proportion of 64% (range: 6% to 89%), indicating high-risk end-stage patients. The patients, aged 3 to 70 years, were enrolled in a “3+3” dose-escalation study. Based on the total dose of RD13-02, they were randomly divided into four dosage groups (DL-1: 0.5×10^8 CAR+T cells; DL1: 2×10^8 CAR+T cells; DL2: 4×10^8 CAR+T cells; DL3: 6×10^8 CAR+T cells). All patients received a standardized lymphodepletion regimen of fludarabine (30mg/m2/day) and cyclophosphamide (500mg/m2/day) for three consecutive days (Day -5 to Day -3) before CAR-T infusion. Preliminary disease assessment was conducted on Day 28. After determining the MTD and RP2D, dose expansion will be carried out.

The study results indicated that no dose-limiting toxicity (DLT), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GVHD) was observed at any dose level. Cytokine release syndrome (CRS) was manageable, mostly mild (G1, n=8; G2, n=2; G3, n=2). Due to the occurrence of Grade 3 CRS in one patient each in the DL2 and DL3 groups, the DL1 dose was set as RP2D, focusing on safety and efficacy. In the initial 28-day evaluation post-infusion, 9 out of 12 patients achieved CR/CRi. By the second month post-infusion, an additional 2 patients achieved CR/CRi, with an ORR of 92%. All patients showed expansion observed through qPCR, with the expansion occurring between Days 6 to 15 and peaking between Days 8 to 27, with a median duration of 33 days (15-79). The study preliminarily confirmed that the anti-CD7 universal CAR-T product RD13-02 is safe and effective for CD7+ R/R T-ALL/LBL. Long-term efficacy needs more patients and extended follow-up for validation. To date, this study has shown the best clinical results for universal CAR-T therapy for R/R T-ALL/LBL, attracting widespread attention from peers both domestically and internationally at this EHA meeting. Additionally, the Bone Marrow Transplantation Center at the First Affiliated Hospital, Zhejiang University School of Medicine is developing multiple targeted CAR-T cell therapy products for various hematologic malignancies, including B-cell, T-cell, and myeloid malignancies.

Current Clinical Treatment of T-ALL/LBL

The treatment of T-ALL/LBL remains a significant clinical challenge. Current strategies involve achieving remission with existing frontline therapies followed by sequential allogeneic or autologous hematopoietic stem cell transplantation, with most patients achieving long-term survival. However, some patients face refractory or relapsed disease with poor prognosis. For these patients, clinical studies of new drugs or treatment strategies, such as innovative drugs based on disease targets and pathways, are actively being conducted but have not achieved significant progress. CAR-T cell therapy, with its excellent efficacy and safety, is currently the most promising innovative therapy. It is hoped that with further research, CAR-T cell therapy can bring more survival benefits to T-ALL/LBL patients.

Challenges and Strategies in CAR-T Cell Therapy

Cellular immunotherapy has been a milestone in the medical field over the past decade, showing breakthrough efficacy in hematologic malignancies, but it still faces several challenges that need to be addressed.

First, the discovery of new targets. Current mature CAR-T cell therapy products mainly focus on B-cell hematologic malignancies, and new targets are urgently needed for T-cell, myeloid, and solid tumors.

Second, improving efficacy. Existing CAR-T cell therapy for B-cell hematologic malignancies has an efficacy rate of about 50%, and continuous technological improvements are expected to develop more effective cell therapy products for clinical application.

Third, existing CAR-T products are autologous CAR-T, which are costly and have long treatment cycles, necessitating the development of universal CAR-T to improve patient compliance.

The team’s novel cell therapy research, including the study selected for this EHA meeting, addresses these clinical challenges. Additionally, last year, the team published results on “function-enhanced” CAR-T in the journal Nature, using PD-1 site-specific integration and non-viral delivery methods to successfully prepare CAR-T cells, significantly enhancing their therapeutic effects.

Furthermore, managing CAR-T cell therapy complications, such as ICANS and CRS, requires in-depth exploration. Progress has been made in understanding the mechanisms of complications, leading to gene functionalization of CAR-T cells and developing “smart” CAR-T products to achieve “efficacy enhancement and toxicity reduction.” Additionally, exploring CAR-T combinations with small molecule targeted drugs and immunotherapeutic drugs could achieve better efficacy. The team recently published in the New England Journal of Medicine on the sequential “integrated” regimen of CD7 CAR-T cell therapy and allogeneic hematopoietic stem cell transplantation (HSCT), showing excellent efficacy in relapsed/refractory hematologic malignancies.

Future Prospects of Cellular Therapy

It is well known that hematology has always been at the forefront of medical development, including the application of the first small molecule targeted drugs and the first antibodies. The remarkable efficacy of cellular therapy in hematologic diseases has demonstrated its great potential in clinical practice. In the future, it is believed that with the development and commercialization of more novel cellular immunotherapy products, their efficacy will continue to improve, side effects will gradually decrease, and indications will expand.

In the field of hematologic diseases, in addition to traditional chemotherapy, small molecule targeted drugs, antibody drugs, and hematopoietic stem cell transplantation, cellular therapy has improved the clinical treatment landscape of hematologic diseases and holds a significant position. It is anticipated that in the future, the treatment of hematologic diseases may enter a chemotherapy-free era, bringing higher cure rates and better quality of life for patients.

🎉🎉To assess whether the condition is suitable for CAR-T or clinic therapy, you can submit Advanced Medicine in China for preliminary evaluation!
WhatsApp: +8613717959070
Email: doctor.huang@globecancer.com

#CAR_T #TALL #LBL #EHA2024 #Immunotherapy #Hematology #CancerResearch #CD7 #CellTherapy #MedicalAdvancements

3 months ago Lymphoma

China’s Breakthrough in CAR-T Therapy for CNS Lymphoma

### China’s Breakthrough in CAR-T Therapy for CNS Lymphoma

Lymphoma

In a pioneering effort to improve outcomes for patients with refractory/relapsed central nervous system lymphoma (CNSL), a multi-center retrospective study led by Professor Jianqing Mi from Ruijin Hospital, Shanghai Jiaotong University School of Medicine, has showcased the impressive real-world effectiveness of Relmacabtagene Autoleucel (Relma-cel). This study, encompassing data from 12 centers across China, represents the largest sample size for a real-world study on commercial CAR-T therapy in treating CNSL, and its results have been recently published in the Journal for ImmunoTherapy of Cancer.

### Study Overview and Patient Demographics

The study included 22 patients aged 18 and above, all diagnosed with CD19+ refractory or relapsed CNSL. These patients had previously undergone various systemic treatments, including CD20 monoclonal antibody immunochemotherapy and high-dose methotrexate-based therapies. Of the participants, 12 had primary CNSL and 10 had secondary CNSL. The median age was 56, with 45.5% being over 60 years old. The study focused on a high-risk group, with many having a Karnofsky Performance Status (KPS) score of ≤60, multiple prior treatment lines, and/or high-risk genetic profiles such as double-hit lymphoma (DHL).

### Treatment and Response

Patients received Relma-cel with a median interval of 32 days between apheresis and infusion. Thirteen patients received a single CAR-T cell infusion, while nine underwent autologous stem cell transplantation (ASCT) in combination with CAR-T infusion. Notably, 20 patients received bridging therapy to control disease before CAR-T infusion. The overall response rate (ORR) was 90.9%, with a complete response (CR) rate of 68.2%. Impressively, all patients achieved CNS response, with 72.7% achieving CNS CR. The median time to response was one month.

### Follow-Up and Survival Outcomes

The median follow-up period was 316 days. Among the 16 patients who achieved CNS response, 81.3% remained alive and in remission, with half maintaining CNS CR for over a year. The study reported a one-year progression-free survival (PFS) rate of 64.4%, duration of response (DOR) rate of 71.5%, and overall survival (OS) rate of 79.2%. Key predictors of better outcomes included achieving CR before infusion and having non-progressive disease at the time of infusion.

### Safety and Tolerability

The safety profile of Relma-cel was acceptable. Cytokine release syndrome (CRS) occurred in 72.7% of patients, primarily grade 1 or 2, with only one case of grade 3. Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 36.4% of patients, mostly grade 1 or 2. There were no CAR-T therapy-related deaths, although five patients (22.7%) died, with three deaths due to disease progression and two from non-relapse causes (COVID-19).

### CAR-T Cell Dynamics and Combined Therapy

The study also explored the pharmacokinetics of CAR-T cells. Relma-cel showed significant expansion in the peripheral blood within the first 28 days post-infusion, with CAR-T cells detected in the cerebrospinal fluid of all evaluable patients. Interestingly, patients receiving additional immunotherapies like BTK inhibitors or PD-1 inhibitors exhibited CAR-T cell re-expansion, suggesting potential synergistic effects.

### Conclusion and Future Directions

This landmark study underscores the clinical efficacy and manageable safety profile of Relma-cel for treating CNSL in a real-world setting. It highlights the potential benefits of combining CAR-T therapy with other immunotherapies, offering a promising strategy for enhancing CAR-T cell persistence and effectiveness. These findings pave the way for future research, suggesting the need for larger, randomized studies to further validate these results and explore the role of CAR-T therapy as a consolidation treatment for high-risk CNSL patients. As China continues to advance in medical research and technology, studies like this are crucial in providing valuable insights and improving global healthcare standards.

🎉🎉To assess whether the condition is suitable for CAR-T or clinic therapy, you can submit Advanced Medicine in China for preliminary evaluation!

WhatsApp: +8613717959070

Email: doctor.huang@globecancer.com

#CARTTherapy #CNSLymphoma #CancerResearch #MedicalBreakthrough #ChinaHealthcare #Immunotherapy #RelmaCel #PatientOutcomes #InnovativeTreatment #ClinicalStudy

3 months ago CAR-T

2024 EHA | New Generation BCL-2 Inhibitor Sonrotoclax Expected to Be a New Treatment Option for RRMM

RRMM

The 29th Annual Meeting of the European Hematology Association (EHA) was held from June 13-16, 2024, in Madrid, Spain. During this event, the results of the study on the new-generation BCL-2 inhibitor Sonrotoclax (BGB-11417) combined with dexamethasone for the treatment of relapsed/refractory multiple myeloma (RRMM) patients with t(11;14) were presented.

Ib/II Phase Study of Sonrotoclax (BGB-11417) Combined with Dexamethasone for the Treatment of RRMM with t(11;14)

Study Background

The B-cell lymphoma-2 (BCL-2) protein helps multiple myeloma (MM) tumor cells evade apoptosis and promote cell survival. Studies have found that MM cells with t(11;14) have significantly higher BCL-2 protein expression compared to other cells. BCL-2 inhibitors can block anti-apoptotic mechanisms and induce cell apoptosis. Currently, data have shown that BCL-2 inhibitors have significant anti-MM potential in RRMM patients with t(11;14) who have failed multiple lines of treatment. However, to date, no BCL-2 targeted therapy has been approved for MM treatment.

Sonrotoclax (BGB-11417) is a new-generation BCL-2 inhibitor. Preclinical studies have found that it has over ten times the BCL-2 inhibitory ability of the first-generation BCL-2 inhibitors, a shorter half-life, and no dose accumulation. BGB-11417-105 (NCT04973605) is an ongoing Ib/II phase trial aimed at evaluating the efficacy and safety of Sonrotoclax combined with dexamethasone ± carfilzomib/daratumumab/pomalidomide in treating RRMM patients with t(11;14). The latest data from this study were reported at this EHA meeting.

Study Design

The enrolled patients were all RRMM with t(11;14), who had failed at least three treatments, including proteasome inhibitors (PI), immunomodulatory drugs (IMIDs), and anti-CD38 monoclonal antibodies, and were refractory/relapsed to the most recent treatment. In the first part, dose escalation cohorts, patients took 80, 160, 320, or 640 mg of Sonrotoclax daily, combined with 40 mg of dexamethasone weekly until intolerance, disease progression, or death. The primary endpoints were safety/tolerability, determining the maximum tolerated dose (MTD)/maximum assessed dose (MAD), and recommending the dose for the expansion phase (RDFE). The second part, dose expansion, primarily evaluated the tolerability and antitumor activity of Sonrotoclax combined with dexamethasone ± carfilzomib/daratumumab/pomalidomide.

Study Results

The initial report at 2023 ASH showed that Sonrotoclax (640 mg) was well tolerated, with no dose-limiting toxicities (DLTs) observed in any patients, establishing 640 mg as the RDFE. The overall response rate (ORR) for this cohort was 70%, and the rate of very good partial response (≥VGPR) was 40%.

Updated in this report: as of March 25, 2024, 32 patients received the RDFE dose of 640 mg Sonrotoclax combined with dexamethasone (10 in the first part and 22 in the second part). The median follow-up time was 4.6 months (0.1-19 months).

The median age of patients was 69 years (48-80 years), with a median of 3 prior lines of treatment (1-12 lines), and 28.1% had high-risk cytogenetic abnormalities. All patients had been exposed to PI and IMiD treatments, and 72% had been exposed to anti-CD38 monoclonal antibody treatments. 56% were PI-refractory, 72% were IMiD-refractory, 56% were anti-CD38 monoclonal antibody-refractory, and 47% were triple-refractory.

Safety

No patients experienced DLTs. The most common treatment-emergent adverse events (TEAEs) were fatigue and insomnia (28% each), diarrhea (22%), constipation, and nausea (16% each). Only 4 patients (13%) experienced hematologic TEAEs (grade 3 thrombocytopenia, grade 1 and 3 platelet count decrease, and grade 3 neutropenia). Two patients died, both unrelated to treatment (one due to pancreatic cancer complications and one due to liver cancer and liver failure).

Efficacy

Among the 24 evaluable patients, the ORR was 75%, with a ≥VGPR rate of 50%. The complete response (≥CR) rate was 21% (CR, n=4; sCR, n=1), with two patients achieving minimal residual disease (MRD) negativity (10^-5). The median time to response was 0.7 months, and the median duration of response (DOR) was 8 months. As of the follow-up, the longest DOR was 18 months.

Conclusion

Sonrotoclax (640 mg) combined with dexamethasone was well tolerated in heavily pretreated RRMM patients with t(11;14), with low rates of hematologic toxicity and infection. It provided deep and durable responses: ORR was 75%, ≥VGPR rate was 50%, and ≥CR rate was 21%. This study will continue to explore Sonrotoclax in combination with other novel agents.

Interpretation by Professor Lu Jin

The t(11;14) translocation is a common genetic abnormality in MM patients, present in approximately 15%-20% of newly diagnosed MM cases. Before the era of novel drugs, many researchers believed that patients with t(11;14) had favorable treatment outcomes and were classified as a standard-risk group. However, recent studies have found that patients with t(11;14) are less sensitive to bortezomib regimens, and even with the VRd regimen, patients with t(11;14) have significantly lower deep response rates (≥VGPR) and PFS benefits compared to other standard-risk patients. This suggests that t(11;14) may be an influencing factor for poor efficacy of novel drugs, necessitating other therapies to improve prognosis.

Studies have found that tumor cells with t(11;14) often have high BCL-2 expression and high sensitivity to BCL-2 inhibitors. The phase III CANOVA study demonstrated that venetoclax combined with dexamethasone resulted in deeper response rates (ORR 62% vs. 35%, p<0.001; ≥VGPR rate 39% vs. 14%, p<0.001) and longer median PFS (9.1 months vs. 4.9 months, p=0.237) compared to pomalidomide combined with dexamethasone in treating RRMM patients with t(11;14), though without significant statistical difference. The failure to meet the primary endpoint might be due to more patients in the control group not reaching IMWG-defined disease progression and thus being treated with new regimens, resulting in censored data in the initial PFS analysis. In the latest post-hoc analysis, including new treatment as an event in PFS, the analysis showed a significant statistical difference in median PFS (9.4 months vs. 4.0 months, p=0.003).

Therefore, the benefits of BCL-2 inhibitors still warrant further exploration. Sonrotoclax is a second-generation highly selective and potent BCL-2 inhibitor. In preclinical trials, Sonrotoclax had an IC50 for BCL-2 protein over ten times lower than that of the first-generation BCL-2 inhibitors (0.014 nM vs. 0.2 nM). It also showed ≥2000 times selectivity over BCL-XL, BCL-W, MCL-1, and BCL2A1 and stronger cytotoxicity against MM cell lines. Additionally, Sonrotoclax has a shorter half-life (approximately 4.5 hours), allowing more flexible exploration of rapid dose escalation plans without the risk of off-target toxicity due to drug accumulation.

The Ib/II phase study reported at this EHA meeting demonstrated that Sonrotoclax combined with dexamethasone was well tolerated in RRMM patients previously treated with multiple lines of therapy. The 640 mg RDFE dose achieved a 75% ORR, ≥VGPR rate of 50%, and ≥CR rate of 21%. We look forward to the release of more results from Sonrotoclax combination therapies. Additionally, as the proportion of t(11;14) in systemic light chain amyloidosis and plasma cell leukemia is higher than in MM, the exploration of BCL-2 inhibitors in these plasma cell diseases is also ongoing.

Professor Lu Jin

Chief Physician, Professor, Ph.D. Supervisor

Peking University People’s Hospital, Peking University Institute of Hematology

Specializes in clinical and laboratory research on multiple myeloma, primary systemic amyloidosis, lymphoma, and cellular immunotherapy.

General Secretary and Standing Committee Member of the Hematology Physician Branch of the Chinese Medical Doctor Association

President of the Hematology Physician Branch of the Beijing Medical Doctor Association

Vice Chairman of the Multiple Myeloma Professional Committee and the Histiocyte Disease Professional Committee of the Chinese Medical Doctor Association

Vice President of the Hematology Branch of the Chinese Society of Geriatrics and Chairman of the Multiple Myeloma Academic Committee

Deputy Leader of the Plasma Cell Group of the Hematology Branch of the Chinese Medical Association

Deputy Leader of the Multiple Myeloma and Related Diseases Professional Group of the Hematology Professional Committee of the Chinese Women Physicians Association

Member of the Chinese and International Primary Systemic Amyloidosis Collaboration Group

Member of the International Myeloma Working Group and the Asia-Pacific Myeloma Working Group

To assess whether the condition is suitable for CAR-T or clinic therapy, you can submit Advanced Medicine in China for preliminary evaluation!

WhatsApp: +8613717959070

Email: doctor.huang@globecancer.com

#Sonrotoclax #RRMM #BCL2Inhibitor #MultipleMyeloma #EHA29 #Hematology #NewTreatment #CancerResearch #2024EHA

3 months ago CAR-T

Sustained 7-Month CR, Liver Extramedullary Disease Disappearance: Equecabtagene Autoleucel Brings High-Quality Survival Hope to Ultra-High-Risk RRMM Patients with Extramedullary Disease

### Sustained 7-Month CR, Liver Extramedullary Disease Disappearance: Equecabtagene Autoleucel Brings High-Quality Survival Hope to Ultra-High-Risk RRMM Patients with Extramedullary Disease

RRMM Patients

In December 2019, a man in his 50s was diagnosed with multiple myeloma (MM) at a hospital in Shenzhen, China. The patient had high-risk cytogenetic abnormalities (17p deletion) and underwent various treatments over more than three years, including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and CD38 monoclonal antibodies. Despite these treatments, the patient experienced a second relapse. This relapse was characterized by a P53 gene mutation and liver extramedullary invasion, classifying it as an ultra-high-risk situation. Although the patient initially refused an autologous stem cell transplant (ASCT), he was eventually persuaded to collect sufficient stem cells. However, due to concerns about the side effects of high-dose chemotherapy, he opted for CAR-T therapy.

### Personalized Treatment: From ASCT to CAR-T Therapy

Under the care of Professor Chen’s team at the hospital, the patient was evaluated for CAR-T therapy. Despite the risks, he underwent the treatment and showed significant improvement. As of March 2024, he has maintained a complete response (CR) for seven months, with PET/CT scans indicating the disappearance of liver extramedullary disease.

#### Patient Background

– Age: 54

– Initial Symptoms: Back pain after exercise

– Diagnosis: Multiple Myeloma (IgA κ type, DS I A stage, ISS I stage, R-ISS II stage, mSMART high-risk)

### Treatment Journey

– 2019: Diagnosed with MM; high-risk cytogenetic abnormality (17p deletion)

– 2020-2022: Treated with PIs, IMiDs, and CD38 monoclonal antibodies

– Early 2023: Second relapse with P53 mutation and liver extramedullary disease

– July 2023: Stem cell collection for ASCT

– August 2023: Initiated CAR-T cell (Equecabtagene Autoleucel) therapy

– September 2023: Discharged with strict complete response (sCR)

– March 2024: PET/CT scan confirms sustained complete response (CR) with no liver lesions

### Breakthrough Results and Future Prospects

CAR-T therapy has emerged as a promising treatment for relapsed and refractory multiple myeloma (RRMM), especially for patients resistant to conventional therapies. This case highlights the importance of personalized treatment plans, considering disease factors, previous treatment outcomes, and patient preferences. Equecabtagene Autoleucel (IKEA-Lunsay) CAR-T therapy has given this high-risk patient a new lease on life and holds the potential to offer hope to many more MM patients in China.

By showcasing such success stories, we aim to raise awareness about the advancements in CAR-T therapy and its significant impact on improving the quality of life for MM patients. This breakthrough not only marks a significant achievement for the hospital but also signals a new era of hope for countless MM patients.

🎉🎉To assess whether the condition is suitable for CAR-T or clinic therapy, you can submit Advanced Medicine in China for preliminary evaluation!

WhatsApp: +8613717959070

Email: doctor.huang@globecancer.com

#MedicalBreakthrough #CARTTherapy #MultipleMyeloma #CancerTreatment #PatientSuccess #HealthcareInnovation #CancerResearch #MMTreatment #LifeSavingTherapies #MedicalAdvancements #HealthcareHeroes #InnovativeMedicine #CancerCare #HopeForMM #CancerAwareness

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Tags Archives: Cancer Research